Approaches for the Identification of New Biomarkers for Alzheimer's Disease

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Alzheimer's disease is the most common form of progressive dementia, currently affecting 17 to 25 million people worldwide. Diagnosis of Alzheimer’s disease (AD) is difficult, expensive and is only late in the disease. The currently best biochemical disease parameters in the cerebrospinal fluid (CSF) are Abeta, Tau, phosphorylated Tau and combinations thereof. However, there is a huge overlap in these markers between healthy controls, AD patients, and patients with other dementias and there is urgent need for the identification of easy and cost effective tests for the early identification of AD. Metabolic profiling offer the prospect of efficiently distinguishing individuals with particular disease or toxic states. Here we show the metabolic profile in human cerebrospinal-fluid (CSF) samples of Alzheimer’s disease (AD) patients and age matched healthy controls. Controls and AD patients had comparable age distribution and derived from five different clinical centers in Europe.The applied combination of different metabolic profiling technologies allowed to identify and quantitate in total 343 analytes in human CSF. From these, 83 metabolites could be structurally identified. By applying univariate and multivariate statistical methods, the metabolite profiling analysis allowed for substantial differentiation of the metabolite profiles between AD patients and healthy controls showing significant differences between the two groups. With this approach we have identified candidates for biomarkers traced to particular metabolites or pathways specific for AD or the underlying neurodegenerative process and to be used as a starting point to for further validation in independent sample sets and subsequent studies.